Upregulated functional gene expression programmes in tumour pericytes mark progression in patients with low-grade glioma.

ABSTRACT

Pericytes conceivably play important roles in the tumour microenvironment of glioblastoma multiforme (GBM) by allowing for an aberrant vasculature and acting as a component in the perivascular niche that supports glioma stem-like cells. However, a lack of specific markers has hampered in-depth elucidation of the functional contribution of pericytes to GBM. This study provides a comprehensive computational biology approach to annotate pericyte marker genes in the GBM vasculature through integration of data from single-cell RNA-sequencing studies of both mouse and human tissue, as well as bulk tumour and healthy tissue gene expression data from patients with GBM. We identified distinct vascular- and immune-related gene expression programmes in tumour pericytes that we assessed for association with GBM characteristics and patient survival. Most compellingly, pericyte gene signatures that were upregulated in tumours compared with normal brain tissue were indicative of progression of low-grade gliomas into high-grade glioma, suggested by a markedly shorter overall survival. Our results underline the functional importance of tumour pericytes in low-grade glioma and may serve as a starting point for efforts for precision targeting of pericytes.